Does the world need another beta blocker? Forest Labs and
Mylan say their newly approved ß-blockade drug, Bystolic, is different. According
to Charles Triano, Forest VP, investor relations, setting the new drug apart
from traditional beta blockers are its greater tolerability, vasodilating
qualities and efficacy in a broader group of patients, including blacks. Those
insights are likely to feature in promotions. Don't look for Forest
to advertise on TV or use other common DTC tactics, though. “The typical Forest model is a lot of physician education right to the
prescriber level,” Triano said. That means some patient outreach via the
Internet, but mostly the firm will rely on physician education from its roughly
2,000 reps detailing Bystolic, as well speaker programs. Another method
preferred by Forest is journal advertising, in
this case through multi-page buys in the minimass publications. The company
will also work with managed care organizations to get the drug covered.

The Market

Beta blockers US sales ($000s) last 5 years

2006

$2,296,910

2005

$2,107,054

2004

$1,899,567

2003

$1,576,975

2002

$1,337,166

Source: IMS Health, Jan. 2008

Top 5 beta blockers

Jan.-June '07 US sales ($000s)

% sales growth over Jan.-June ‘06

TOPROL-XL (AstraZeneca)

$760,938

-10%

METOPROLOL SUCCIN

$89,141

***

PROPRANOLOL HCL

$63,994

508%

INDERAL LA (Wyeth)

$46,914

-57%

ATENOLOL

$42,012

-29%

Source: IMS Health, Jan. 2008

Physician Outlook

Nebivolol (Bystolic) is a new beta blocker expected to
launch early in 2008. Forest, which licensed
the product from Mylan in 2006, plans to introduce this new hypertension
treatment in a market already crowded with generic options, including generic
beta blockers. Forest believes that despite
the cost pressures, Bystolic's low sedation level will be the competitive advantage
that drives its use. According to GfK Market Measures 2007 Treatment of
Hypertension Physician research, of the 20% of beta blocker users who have a
problem with side effects, fatigue is the number-one complaint. Nebivolol is
currently in Phase III research as well for treatment of heart failure.

Nebivolol is a once-daily ß-adrenergic blocking agent that, at doses up to 10mg, is primarily ß1-selective. In poor metabolizers (those with reduced activity of CYP2D6) and at higher doses, however, it may inhibit ß2 adrenergic receptors as well. ß2
blockade may lead to bronchoconstrictive effects. Nebivolol does not
have intrinsic sympathomimetic effects or membrane stabilizing activity
at therapeutic doses. It has several active metabolites which are the
product of glucuronidation and hydroxylation by the oxidative enzyme
CYP2D6.

Three double-blind, placebo-controlled, 12-week studies were conducted
to demonstrate the effectiveness of nebivolol as monotherapy in the
treatment of hypertension. Two of these trials studied 1716 patients in
the general hypertensive population (26% non-Caucasian) and a third
studied 300 Black (African-American) patients. Another study, which
enrolled 669 patients, evaluated the effect of adding nebivolol to a
background anti-hypertensive regimen of up to two other agents,
including ACEIs, ARBs, and thiazide diuretics. In each study, nebivolol
was shown to be effective in lowering both systolic and diastolic BP.
Effectiveness was established in Black patients, but as monotherapy the
magnitude of effect was somewhat less than in Caucasians. The
BP-lowering effect was seen at 2 weeks after starting therapy and was
maintained over the 24-hour dosing interval.